AMYLOID b BINDING TO LIPIDS AND APOLIPOPROTEINS OF THE HDL

N.V. Koudinova^1,2, A.R. Koudinov^1,2,  A. Kumar² and T.T. Berezov¹

1. Russian Academy of Medical Sciences, National Mental Health Research Center, Institute of Biomedical Chemistry, Timoshenko 38-27, Moscow 121359, Russian Federation

2. Department of Pathology and Medicine, New York University Medical Center, 560 First Avenue, New York, NY 10016, USA

   It is known that in normal human plasma1 and cerebrospinal fluid (1-3) the soluble form of Alzheimer's amyloid beta protein (sAb) is complexed to high density lipoprotein (HDL) and that Ab protein participates in lipid metabolism (4, 5). Nevertheless, it is not known to which HDL structural constituent sAb is primarily bound. Herein we report further studies of the Ab to HDL interaction in an in vitro system using biotinylated synthetic Ab1-40 as an sAb tracer and normal human plasma HDL. Purified HDLs were incubated with the peptide followed by the lipoprotein repurification by Size Exclusion (SE) HPLC. SDS/ PAGE followed by Immunoblot and N-terminal sequence analysis of the biotin-Ab positive protein bands revealed that Ab is bound to many apolipoproteins of the HDL, mainly apoA-I, apoA-II, apoE and apoJ.  On the other hand, reconstituted protein free HDL also binds Ab peptide and inhibits its aggregation, as intact HDL does. This was assessed by SE-HPLC, SDS/PAGE, Immunoblot analysis and ultrastructural electron microscopic studies of Ab morphology and Congo Red staining for b amyloid fibrils. Ab binding to both lipids and apolipoproteins may modulate the peptide to HDL association (2, 3) and be particularly relevant to Ab biochemistry, physiology (4, 5) and the disease.

REFERENCES:
1. Koudinov A., Matsubara E., Frangione B., Ghiso J., The Soluble Form of Alzheimer's Amyloid Beta Protein is Complexed to High Density Lipoprotein 3 and Very High Density Lipoprotein in Normal Human Plasma. Biochem Biophys Res Commun 1994; 205: 1164-1171.

2. Koudinov A., Koudinova N., Kumar A., Beavis R., Ghiso J., Biochemical characterization of Alzheimer's soluble amyloid beta protein in human cerebrospinal fluid: association with high density lipoproteins. Biochem Biophys Res Commun. 1996; 223: 592-597.

3. Koudinov A., Koudinova N., Kumar A., Beavis R., Ghiso J., Alzheimer's soluble amyloid beta protein is associated with high density lipoproteins in normal human cerebrospinal fluid and is secreted by HepG2 cells as a part of lipoprotein complexes. Soc Neurosci Abst. 1996; 22: 2118.

4. Koudinov A., Koudinova N., Berezov, T., Alzheimer's Ab1-40 and Ab1-28 inhibit the plasma cholesterol esterification rate. Biochem Mol Biol Internat 1996; 38: 747-752.

5. Koudinova N., Berezov T., Koudinov, A. Multiple inhibitory effect of Alzheimer's Ab1-40 on lipid byosynthesis in HepG2 cells. FEBS Lett 1996; 395: 204-206.

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